Preparation of acylcyclohexadionethiocarboxylic s-esters

ABSTRACT

An acylcyclohexadionethiocarboxylic S-ester of the fomrula ##STR1## where R 1  and R 2  are substituted or unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, benzyl or phenyl, and R 2  is additionally hydrogen, are prepared by reacting an acylcyclohexadione II ##STR2## with hydroxylamine or hydroxylamine-O-sulfonic acid in an inert solvent at from 0° to 150° C., to give an acylcyclohexadione compound III ##STR3## and then reacting the compound III with a mercaptan IV 
     
         R.sup.2 --SH                                               IV 
    
     in the presence of an anhydrous acid HX to give an acylcyclohexadionethiocarboximidic S-ester salt V ##STR4## where X is the anion of the acid, and hydrolyzing the compounds V to the acylcyclohexadionethiocarboxylic S-ester I.

The present invention relates to the preparation ofacylcyclohexadionethiocarboxylic S-esters of the formula I ##STR5##where R¹ is C₁ -C₂₀ -alkyl, C₂ -C₂₀ -alkenyl, C₂ -C₂₀ -alkynyl or C₃ -C₆-cycloalkynyl each of which is unsubstituted or substituted by halogen,C₁ -C₄ -alkoxy or C₁ -C₄ -alkylthio, or is benzyl or phenyl, each ofwhich is unsubstituted or substituted by halogen, cyano, C₁ -C₄ -alkyl,C₁ -C₄ -alkoxy, C₁ -C₄ -haloalkyl or nitro, and R² is hydrogen, C₁ -C₆-alkyl, C₂ -C₆ -alkenyl, C₂ -C₆ -alkynyl or C₃ -C₆ -cycloalkyl, each ofwhich is unsubstituted or substituted by C₁ -C₄ -alkoxy, C₁ -C₄-alkylthio, C₁ -C₄ -dialkylamino, hydroxyl or halogen; benzyl or phenyl,each of which is unsubstituted or substituted by halogen, cyano, C₁ -C₄-alkyl, C₁ -C₄ -alkoxy or nitro.

Furthermore, novel intermediates are made available by the presentinvention.

Acylcyclohexadionethiocarboxylic S-esters I are highly activebioregulators, as is disclosed in EP-A 293 817. There are variouspossibilities for the preparation of S-esters. Some methods aredescribed below.

Route A:

S-exters are prepared from activated carboxylic acids with thiols.Examples of suitable activating reagents are diphenylphosphinic chloride(Monatsh. Chem. 110, (1979) 759), diethyl cyanophosphate (TetrahedronLett. 1973, 1595), carbonyl-bis-imidazolide and carbonyl-bis-triazolide(Angew. Chem. 89 (1977) 251; J. Am. Chem. Soc. 93 (1971) 1419).

Route B:

S-esters are prepared from carbonyl halides or carboxylic anhydrides oresters with thiols or thiolates in the presence or absence of a base(Houben-Weyl, Methoden der organischen Chemie, Vol. 9, pages 753-760,1955).

Route C:

S-esters are prepared by free-radical substitution on aldehydes withorganic disulfides catalyzed by UV light or with free radical initiatorssuch as azobisisobutyronitrile (Bull. Chem. Soc. Jpn. 53, (1980), 1982).

All of these processes have one or more serious disadvantages. Theactivating reagents used in route A are costly or difficult to obtain,which rules out commercial utilization. The aldehyde component is usedin large excess or as solvent in route C, which makes the processuneconomic for costly aldehydes.

Route B, the reaction with acid halides or anhydrides, is a standardmethod for preparing S-esters. However, there is a risk with thecyclohexadiones that the conventional halogenating agents such asthionyl chloride, phosphorus oxychloride, sulfuryl chloride, oxalylchloride or phosgene will also replace the vinylic OH group by halogen,e.g. chlorine or bromine.

It is also known from the literature that adducts are formed betweenmercaptans and nitriles in the presence of hydrogen chloride. Theresulting thiocarboximidic S-esters can be hydrolyzed to thiocarboxylicS-esters (A. Pinner, Die Iminoether, p. 80 Verlag R. Oppenheim, Berlin1892). However, because of the competing hydrolysis to carboxamides andcarboxylic acids, in general, yields of only about 10 to 25% areobtained (see, for example, U.S. Pat. No. 2,458,075 (1946) PhilippsPetrol Co., inventor: Ch. M. Himel, CA 43 (1949) 3444 or Ber. Dt. Chem.Ges. 69 (1936) 2352), for which reason this sequence of reactions is notregarded as being of preparative significance (Houben-Weyl, Methoden derorganischen Chemie, E5/I p. 876, 1985).

It is an object of the present invention to find a process for preparingthe acylcyclohexadionethiocarboxylic S-esters I, which are defined inthe first paragraph, which is straightforward and can be carried out onan industrial scale, gives good yields of the desired product I andrequires few process stages.

We have found that this object is achieved by a process for preparingacylcyclohexadionethiocarboxylic S-esters of the formula I ##STR6##where R¹ is C₁ -C₂₀ -alkyl, C₂ -C₂₀ -alkenyl, C₂ -C₂₀ -alkynyl or C₃ -C₆-cycloalkyl, each of which is unsubstituted or substituted by halogen,C₁ -C₄ -alkoxy or C₁ -C₄ -alkylthio, or is benzyl or phenyl, each ofwhich is unsubstituted or substituted by halogen, cyano, C₁ -C₄ -alkyl,C₁ -C₄ -alkoxy, C₁ -C₄ -haloalkyl or nitro, and

R² is hydrogen, C₁ -C₆ -alkyl, C₂ -C₆ -alkenyl, C₂ -C₆ -alkynyl or C₃-C₆ -cycloalkyl, each of which is unsubstituted or substituted by C₁ -C₄-alkoxy, C₁ -C₄ -alkylthio, C₁ -C₄ -dialkylamino, hydroxyl or halogen;benzyl or phenyl, each of which is unsubstituted or substituted byhalogen, cyano, C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy or nitro, which comprisesreacting, in a first stage, a compound of the formula II ##STR7## whereR¹ has the abovementioned meaning, with hydroxylamine orhydroxylamine-O-sulfonic acid in an inert solvent at from 0° to 150° C.to give a compound of the formula III ##STR8## where R¹ has theabovementioned meaning, and then, in a second stage, reacting this cyanocompound of the formula III with a mercaptan of the formula IV

    R.sup.2 --SH                                               IV

where R² has the abovementioned meaning, in the presence of an acid HX,to give a compound of the formula V ##STR9## where R¹ and R² have theabovementioned meanings, and X is the anion of an acid, and, in a thirdstage, hydrolyzing the compound of the formula V to give the compound ofthe formula I.

The reaction sequence in the process according to the invention is shownin the scheme below, where R¹ is methyl, R² is ethyl and the acid usedin the second stage is hydrogen chloride.

Reaction scheme: ##STR10##

In the first stage, the formyl compound II, which can be obtained asdescribed in DE-A-233,568, is reacted with hydroxylamine-O-sulfonic acidor hydroxylamine under condensation conditions in an inert solvent atfrom 0° to 150° C., in particular 20° to 80° C. It has provenparticularly beneficial to carry out the reaction withhydroxyl-amine-O-sulfonic acid in water, e.g. in from 1 to 100 parts byweight of water based on the formyl compound II.

The reaction can be carried out in homogeneous or heterogeneous aqueousphase, with or without the addition of a buffer, the pH generally beingfrom 1 to 9, in particular from 3 to 8.

The procedure is expediently such that the formyl compound II issuspended or induced to dissolve, by adding a water-miscible organicsolvent, e.g. methanol or ethanol, in water. It is also possible todissolve the starting material II in water-immiscible solvents such asethers, e.g. diethyl ether, chlorohydrocarbons such as methylenechloride, chloroform or dichloroethane, esters such as ethyl acetate, oraromatic compounds such as benzene, toluene or xylenes. Thehydroxylamine-O-sulfonic acid is added in solid form or as aqueoussolution to the mixture of solvent and starting material II.

If the reaction is carried out in heterogeneous phase, it isadvantageous to ensure that the phases are thoroughly mixed.

In order to achieve complete conversion into the cyano compound III, itis advisable to employ the reactants in equimolar amounts. It may beadvisable, for technical reasons, to employ the formyl compound II orthe hydroxylamine-O-sulfonic acid in an excess of, for example, from 1to 100 mol %. It is preferable to use the hydroxylamine-O-sulfonic acidin an excess of from 10 to 20 mol %.

As a rule, the reaction goes to completion at up to 60° C., inparticular from 20° to 40° C.

It may be advantageous in some cases to increase the reaction rate byadding catalytic amounts of a base.

Examples of suitable bases are alkali metal hydroxides such as NaOH orKOH, ammonium hydroxide, alkaline earth metal hydroxides such asmagnesium hydroxide or calcium hydroxide, alkali metal carbonates orbicarbonates such as potassium carbonate or sodium bicarbonate. It isnormally possible to use, based on the starting material II, from 0 to 3equivalents of base.

The reaction can be carried out under atmospheric pressure or elevatedor reduced pressure, continuously or batchwise, using the conventionaltechniques.

The cyanocyclohexenone compound III can be isolated from the crudereaction mixture in a conventional manner, e.g. by extraction orfiltration.

It is also possible to react the starting material II with hydroxylaminein place of hydroxylamine-O-sulfonic acid, and then to eliminate waterin a conventional manner, e.g. by heating with acetic anhydride orthionyl chloride at from about 80° to 150° C.

In the second stage, the acylcyclohexadione III is reacted with amercaptan R² -SH IV in the presence of anhydrous acid and with exclusionof water. Examples of such acids are hydrogen chloride, hydrogenbromide, sulfuric acid, perchloric acid or tetrafluoroboric acid orstrong carboxylic acids such as trifluoroacetic acid. Particularpreference is given to hydrogen bromide and, in particular, hydrogenchloride.

In order to achieve complete conversion, it is advisable to employ themercaptan IV and the cyano compound III in equimolar amounts. It may beadvantageous, for technical reasons, to employ one of the two componentsin excess. The mercaptan is preferably used in an excess of from 0 to200 mol %, preferably from 5 to 100 mol %.

Preferred R² radicals in the mercaptan are: methyl, ethyl, propyl,i-propyl, t-butyl, n-hexyl, allyl, butenyl, methoxyethyl,3-chloropropyl, 2-dimethylaminoethyl, 2-hydroxyethyl, cyclohexyl,benzyl, 4-methylbenzyl, 4-chlorobenzyl, phenyl, p-tolyl, 4-chlorophenyl,4-methoxyphenyl, 3-nitrophenyl.

The reaction of the cyanocyclohexadione compound III with the mercaptanIV is expediently carried out in an aprotic organic diluent. Suitableexamples are ethers such as diethyl ether, tetrahydrofuran and dioxane,hydrocarbons such as pentane, hexane, cyclohexane, petroleum etherbenzene and toluene, halohydrocarbons such as methylene chloride,chloroform, tetrachloromethane and 1,2-dichloroethane.

The reaction can be carried out at from -20° C. to 100° C., preferablyfrom 0° C. to +40° C., under atmospheric pressure or elevated or reducedpressure, using the conventional techniques.

The reaction is expediently carried out in such a way that thecyanocyclohexadione compound III is introduced together with themercaptan IV into the diluent, substantially excluding water, and theacid is added dropwise or passed in as gas at low temperature, e.g. 0°C. It is then possible, to complete the reaction, to warm to from 20° to40° C., for example.

The carboximidic S-ester salt V, which generally separates out ascrystals or an oil, can be isolated in a conventional manner, e.g. byfiltration or extraction. If there is no interest in isolating theintermediates V, these can be converted by aqueous extraction, withsimultaneous hydrolysis, into the final products I.

The intermediates V can be hydrolyzed in water, preferably in thepresence of an acid or, in particular, in dilute aqueous mineral acid,e.g. hydrochloric, sulfuric or phosphoric acid, or dilute carboxylicacids such as acetic or formic acid.

The amount of acid is not particularly critical and is generally from 0to 100 parts by weight of acid based on V. The acid concentration isfrom 0 to 20% by weight, and aqueous solutions containing from 0 to 10%by weight of acid are preferably used. The pH of the reaction mixture ispreferably from 1 to 7, in particular below 2.

The reaction temperatures are likewise not critical and are usually from0° to 100° C., in particular from 10 to 40° C.

Because the S-esters of the formula I are not soluble in water(solubility 100 mg/1), they are produced in the hydrolysis of V as anoil or solid. The hydrolysis can take place in a two-phase system byadding a water-immiscible solvent such as an ether, e.g. diethyl ether,ester, e.g. ethyl acetate, chlorohydrocarbon, e.g. methylene chloride,chloroform, tetrachloromethane or dichloroethane, aromatic hydrocarbon,e.g. benzene, toluene or xylene, which has the advantageous result thatthe reaction product I can be isolated directly from the organic phase.It is, of course, also possible to add the organic solvent only afterthe hydrolysis has taken place, in order to isolate I.

Otherwise, the process, which can also be carried out as a one-potprocess without isolation of the intermediates III and V described,involves no special technical procedures.

The invention provides novel intermediates V.

The acylcyclohexadionecarboximidic S-ester salts V have the followingformula ##STR11## where R¹ is C₁ -C₂₀ -alkyl, C₂ -C₂₀ -alkenyl, C₂ -C₂₀-alkynyl or C₃ -C₆ -cycloalkyl, each of which is unsubstituted orsubstituted by halogen, C₁ -C₄ -alkoxy or C₁ -C₄ -alkylthio, or isbenzyl or phenyl, each of which is unsubstituted or substituted byhalogen, cyano, C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy, C₁ -C₄ -haloalkyl ornitro;

R² is hydrogen, C₁ -C₆ -alkyl, C₂ -C₆ -alkenyl, C₂ -C₆ -alkynyl or C₃-C₆ -cycloalkyl, each of which is unsubstituted or substituted by C₁ -C₄-alkoxy, C₁ -C₄ -alkylthio, C₁ -C₄ -dialkylamino, hydroxyl or halogen;benzyl or phenyl, each of which is unsubstituted or substituted byhalogen, cyano, C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy or nitro, and

X is a chloride, bromide, sulfate, phosphate, tetrafluoroborate,perchlorate or trifluoroacetate ion.

With a view to the biological activity of the final products I, R¹, R²and X in the formula V have the following preferred meanings:

R¹

C₁ -C₆ -alkyl such as methyl, ethyl, propyl, isopropyl, n-butyl,iso-butyl, s-butyl, t-butyl, n-pentyl, n-hexyl

C₃ -C₆ -cycloalkyl such as cyclopropyl, cyclopentyl, cyclohexyl

C₂ -C₆ -alkoxyalkyl e.g. C₁ -C₄ -alkoxy-C₁ -C₄ -alkyl such asmethoxymethyl, ethoxymethyl, propyloxymethyl, 2-methoxyethyl,2-ethoxyethyl, 2-propyloxyethyl, methoxypropyl, ethoxypropyl,

C₂ -C₆ -alkylthioalkyl, e.g. methylthiomethyl,ethylthiomethyl,methylthioethyl,ethylthioethyl, methylthiopropyl,ethylthiopropyl,

benzyl or phenyl, it being possible for the aromatic nuclei to besubstituted from once to three times by halogen such as chlorine,bromine or fluorine, by cyano, nitro, C₁ -C₄ -alkyl such as methyl,ethyl, propyl or butyl, C₁ -C₄ -alkoxy such as methoxy, ethoxy, propoxyor butoxy, C₁ -C₄ -haloalkyl such as trifluoromethyl,difluorochloromethyl, difluoromethyl, trichloromethyl ortetrafluoroethyl,

R²

C₁ -C₆ -alkyl such as methyl, ethyl, propyl, isopropyl, n-butyl,iso-butyl, sec.-butyl, n-pentyl or n-hexyl,

C₃ -C₅ -alkenyl such as allyl, 2-butenyl, 3-butenyl or 2-pentenyl,

C₃ -C₄ -alkynyl such as propargyl, 2-butynyl or 3-butynyl,

C₃ -C₆ -cycloalkyl as specified for R¹,

C₂ -C₆ -alkoxyalkyl or alkylthioalkyl, in each case as specified for R¹,

phenyl or benzyl, it being possible for the aromatic nuclei to besubstituted as specified for R¹,

chloride or bromide.

It is particularly preferred for R¹ to be C₁ -C₄ -alkyl, C₃ -C₆-cycloalkyl or phenyl, R² to be C₁ -C₆ -alkyl, C₃ -C₄ -alkenyl, C₃ -C₄-alkynyl, C₂ -C₆ -alkoxyalkyl or benzyl, and X to be chloride.

EXAMPLE 1.1 3,5-Dioxo-4-acetylcyclohexanecarbonitrile

19.3 g (0.11 mol) of 5-formyl-2-acetylcyclohexane-1,3-dione wereintroduced into 200 ml of distilled water and, at room temperature, 14.7g (0.13 mol) of hydroxylamine-O-sulfonic acid were added. The mixturewas then stirred at room temperature for 17 h. The precipitate wasfiltered off with suction, washed with water and dried. 11.5 g (61% oftheory) of 3,5-dioxo-4-acetylcyclohexanecarbonitrile were obtained(melting point 94 to 97° C.).

EXAMPLE 1.2 3,5-Dioxo-4-propionylcyclohexanecarbonitrile

30.7 g (0.16 mol) of 5-formyl-2-propionylcyclohexane-1,3-dione wereintroduced into 150 ml of distilled water and, at room temperature, 21.0g (0.19 mol) of hydroxylamine-O-sulfonic acid were added. The mixturewas then stirred at room temperature overnight. The precipitate wasfiltered off with suction, washed with water and dried. 23.8 g (71% oftheory) of 3,5-dioxo-4-propionylcyclohexanecarbonitrile were obtained(melting point 70° to 74° C.).

EXAMPLE 1.5

3,5-Dioxo-4-palmitoylcyclohexanecarbonitrile

43 g (0.12 mol) of 5-formyl-2-palmitoylcyclohexane-1,3-dione weresuspended in 150 ml of distilled water. To this were added 15.7 g (0.14mol) of hydroxylamine-O-sulfonic acid dissolved in 50 ml of water. Theheterogeneous reaction mixture was stirred at room temperatureovernight. The resulting solid was filtered off with suction, washedwith water and dried. 37.7 g (86% of theory) of3,5-dioxo-4-palmitoylcyclohexanecarbonitrile were isolated (meltingpoint 66° to 69° C.).

The cyclohexenone compounds III shown in Table 1 can be prepared in asimilar manner.

                  TABLE 1                                                         ______________________________________                                        Cyclohexenone compounds III                                                    ##STR12##                     III                                                                phys. data                                                No.   R.sup.1       m.p. [°C.] .sup.1 H-NMR [δ in                ______________________________________                                                            ppm]                                                      1.1   methyl        94 to 97                                                  1.2   ethyl         70 to 74                                                  1.3   propyl        47 to 50                                                  1.4   butyl         58 to 59                                                  1.5   pentadecanyl  66 to 69                                                  1.6   cyclopropyl   1.2(m); 1.35(m); 3.0(m); 3.3(m)                           1.7   cyclohexyl                                                              1.8   phenyl                                                                  1.9   4-Cl, 2-NO.sub.2C.sub.6 H.sub.3                                                             184 to 187                                                                    (decomposition)                                           ______________________________________                                    

EXAMPLE 2.1

S-Methyl 3,5-dioxo-4-propionylcyclohexanethiocarboximidate hydrochloride

5.0 g (0.026 mol) of 3,5-dioxo-4-propionylcyclohexanecarbonitrile and1.37 g (0.028 mol) of methyl mercaptan were dissolved in 100 ml of drydiethyl ether. The solution was cooled to 0° C. and then a vigorousstream of dry hydrogen chloride was passed through it. After 0.5 h thegas stream was turned off, and the reaction mixture was slowly warmed toroom temperature. It was again cooled to 0° C., hydrogen chloride waspassed in (0.5 h) and then the cooling was removed and the mixture wasleft to stand overnight. The crystals which formed were filtered offwith suction and dried in vacuo: 5.4 g (74% of theory) of compound 2.1[melting point 161° C. (decomposition)].

EXAMPLE 2.2 S-Ethyl 3,5-dioxo-4-propionylcyclohexanethiocarboximidatehydrochloride

19.3 g (0.1 mol) of 3,5-dioxo-4-propionylcyclohexanecarbonitrile and 6.5g (0.105 mol) of ethyl mercaptan were dissolved in 800 ml of dry diethylether and reacted with hydrogen chloride as described in Example 2.1:20.7 g (71% of theory) of compound 2.2 [melting point 180°-185° C.(decomposition)].

EXAMPLE 2.3 S-Ethyl 3,5-dioxo-4-palmitoylcyclohexanethiocarboximidatehydrochloride

7.5 g (0.02 mol) of 3,5-dioxo-4-palmitoylcyclohexanecarbonitrile and1.86 g (0.03 mol) of ethylmercaptan were suspended in 150 ml of drydiethyl ether. The suspension was cooled to 0° C. and then a vigorousstream of dry (concentrated sulfuric acid) hydrogen chloride was passedthrough it. After 0.5 h the stream of gas was turned off, and thereaction mixture was slowly warmed to room temperature. It was againcooled to 0° C., hydrogen chloride was passed in, the cooling wasremoved and, after a total of 6 h, the solid was filtered off, washedwith ether and dried: 7.3 g (77% of theory) of compound 2.3 [meltingpoint 65°-68° C. (decomposition)].

The carboximidic S-esters V listed in Table 2 can be prepared in asimilar manner.

                  TABLE 2                                                         ______________________________________                                        Acylcyclohexadionethiocarboximidic S-esters V                                  ##STR13##                     V                                              No.  R.sup.1    R.sup.2     X   phys. data m.p. (°C.)                  ______________________________________                                        2.1  ethyl      methyl      Cl  161 (decomp.)                                 2.2  ethyl      ethyl       Cl  180 to 185 (decomp.)                          2.3  palmitoyl  ethyl       Cl  65-68                                         2.4  methyl     ethyl       Cl  160 to 165 (decomp.)                          2.5  ethyl      2-methoxyethyl                                                                            Cl  oil                                           2.6  cyclopropyl                                                                              2-methoxyethy                                                                             Cl  oil                                           ______________________________________                                    

EXAMPLE 3.1 S-Methyl-3,5-dioxo-4-propionylcyclohexanethiocarboxylate

2.8 g (0.01 mol) of compound 2.1 were dissolved in 50 ml of 10% strengthhydrochloric acid and stirred at room temperature overnight. The whiteprecipitate was filtered off, washed with water and dried under reducedpressure: 1.95 g (80% of theory) of compound 3.1 (melting point 81° C.).

EXAMPLE 3.2 S-Ethyl 3,5-dioxo-4-propionylcyclohexanethiocarboxylate

5.8 g (0.02 mol) of compound 2.2 were dissolved in 100 ml of 10%strength hydrochloric acid and stirred at room temperature overnight.The white precipitate was filtered off, washed with water and driedunder reduced pressure: 4.1 g (80% of theory) of compound 3.2 (meltingpoint 70° C.).

EXAMPLE 3.3 S-Ethyl 3,5-dioxo-4-palmitoylcyclohexanethiocarboxylate

3.0 g (6.3 mmol) of compound 2.3 were suspended in 50 ml of water andstirred vigorously at room temperature overnight. The solid was filteredoff, washed with water and dried under reduced pressure: 2.4 g (86% oftheory) of compound 3.3 (melting point 56°-58° C.).

The compounds I listed in Table 3 which follows were prepared in asimilar manner.

                  TABLE 3                                                         ______________________________________                                        Cyclohexanethiocarboxylic S-esters I                                           ##STR14##                     I                                                                               phys. data,                                  No.   R.sup.1        R.sup.2     m.p. (°C.)                            ______________________________________                                        3.1   ethyl          methyl      81                                           3.2   ethyl          ethyl       70                                           3.3   palmitoyl      ethyl       56 to 58                                     3.4   methyl         ethyl                                                    3.5   ethyl          2-methoxyethyl                                                                            oil                                          3.6   cyclopropyl    ethyl       oil                                          3.7   cyclopropyl    2-methoxyethyl                                                                            oil                                          3.8   4-Cl, 2-NO.sub.2C.sub.6 H.sub.3                                                              Ethyl       oil                                          ______________________________________                                    

We claim:
 1. A process for preparing an acylcyclohexadionethiocarboxylicS-ester of the formula I ##STR15## where R¹ is C₁ -C₂₀ -alkyl, C₂ -C₂₀-alkenyl, C₂ -C₂₀ -alkynyl or C₃ -C₆ -cycloalkyl, each of which isunsubstituted or substituted by halogen, C₁ -C₄ -alkoxy or C₁ -C₄-alkylthio, or is benzyl or phenyl, each of which is unsubstituted orsubstituted by halogen, cyano, C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy, C₁ -C₄-haloalkyl or nitro, andR² is hydrogen, C₁ -C₆ -alkyl, C₂ -C₆ -alkenyl,C₂ -C₆ -alkynyl or C₃ -C₆ -cycloalkyl, each of which is unsubstituted orsubstituted by C₁ -C₄ -alkoxy, C₁ -C₄ -alkylthio, C₁ -C₄ -dialkylamino,hydroxyl or halogen; benzyl or phenyl, each of which is unsubstituted orsubstituted by halogen, cyano, C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy ornitro,which comprises reacting, in a first stage, a compound of theformula II ##STR16## where R¹ has the abovementioned meaning, withhydroxylamine or hydroxylamine-O-sulfonic acid in an inert solvent atfrom 0° to 150° C. to give a compound of the formula III ##STR17## whereR¹ has the abovementioned meaning, and then, in a second stage, reactingthis cyano compound of the formula III with a mercaptan of the formulaIV

    R.sup.2 --SH                                               IV

where R² has the abovementioned meaning, in the presence of an anhydrousacid HX, to give a compound of the formula V ##STR18## where R¹ and R²have the abovementioned meanings, and X is the anion of an acid, and, ina third stage, hydrolyzing the compound of the formula V to give thecompound of the formula I.
 2. The process of claim 1, in the first stageof which compound I is reacted with hydroxylamine-O-sulfonic acid inhomogeneous or heterogeneous aqueous phase at a, pH of from 1 to
 9. 3.The process of claim 1, wherein the reaction withhydroxylamine-O-sulfonic acid is carried out at a pH of from 3 to
 8. 4.The process of claim 1, wherein the reaction in the first stage iscarried out at from 20° to 80° C.
 5. The process of claim 1, wherein theacid used in the second stage is hydrogen chloride or hydrogen bromide.6. The process of claim 1, wherein the reaction in the second stag iscarried out at from -20° to 100° C.
 7. The process of claim 1, whereinthe hydrolysis of compound V is carried out at a pH of from 1 to 7 andat from 0° to 100° C.
 8. The process of claim 1, wherein stages 1 to 3are carried out without isolation of the intermediates III and V.